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| United States Patent |
5,342,557
|
|
Kennedy
|
*
August 30, 1994
|
Process for preparing polymer particles
Abstract
A process is provided for preparing particles of polymer by heating the
polymer having an inherent viscosity not exceeding about 0.6 dl/g when
measured at a temperature of about 30.degree. C. in chloroform or
hexafluoroisopropanol, dividing the heated polymer into particles, and
then solidifying these particles such that substantially no fibers are
formed among the particles.
| Inventors:
|
Kennedy; John (Stratford, CT)
|
| Assignee:
|
United States Surgical Corporation (Norwalk, CT)
|
| [*] Notice: |
The portion of the term of this patent subsequent to September 2, 2009
has been disclaimed. |
| Appl. No.:
|
618652 |
| Filed:
|
November 27, 1990 |
| Current U.S. Class: |
264/8; 264/13 |
| Intern'l Class: |
B29B 009/00; B29B 009/02; B29B 009/10; B29B 009/12 |
| Field of Search: |
264/8,11,14,13
425/8
|
References Cited
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| |
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| 4801739 | Jan., 1989 | Franz et al. | 560/185.
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| 4810775 | Mar., 1989 | Bendix et al. | 528/480.
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| 5004602 | Mar., 1991 | Hutchinson | 514/2.
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| |
| 5015423 | May., 1991 | Eguchi et al. | 264/9.
|
| 5015667 | May., 1991 | Yoshimura et al. | 521/58.
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| |
| 5019400 | May., 1991 | Gombotz et al. | 428/402.
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| 5047180 | Sep., 1991 | Steiner et al.
| |
| 5047450 | Sep., 1991 | Wilder | 523/435.
|
| 5080994 | Jan., 1992 | Breton et al. | 430/137.
|
| 5102983 | Apr., 1992 | Kennedy.
| |
| 5108508 | Apr., 1992 | Rademachers et al. | 106/437.
|
| 5128114 | Jul., 1992 | Schwartz | 423/335.
|
| 5143662 | Sep., 1992 | Chesterfield et al. | 264/8.
|
| 5160745 | Nov., 1992 | DeLuca et al. | 424/487.
|
| Foreign Patent Documents |
| 0052793 | Jun., 1982 | EP.
| |
| 265906 | May., 1988 | EP.
| |
| 274898 | Jul., 1988 | EP.
| |
| 0488218 | Jun., 1992 | EP.
| |
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| |
| 2121203 | Dec., 1983 | GB.
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| 2246571 | Feb., 1992 | GB.
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| |
Other References
Search Report from European Application No. 91120279 (26 Jun. 1992).
Search Report from European Appln. No. 92102262.0 (14 Sep. 1992).
NASA Tech Briefs, Sep. 1987, p. 50.
J. Microencapsulation, 1988; vol. 5, No. 2, 147-157.
|
Primary Examiner: Kight, III; John
Assistant Examiner: Mullis; Jeffrey Culpeper
Claims
What is claimed is:
1. Process for preparing particles of bioabsorbable polymer, comprising:
a) heating to a temperature from about 60.degree. to about 300.degree. C.,
a polymer derived from monomers selected from the group consisting of
glycolic acid, lactic acid, dioxanone, e-caprolactone and trimethylene
carbonate and having an inherent viscosity between about 0.5 and about 0.6
dl/g when measured at a temperature of about 30.degree. C. in chloroform
or hexafluoroisopropanol, to form a molten or flowable mass;
b) dividing the molten or flowable mass of thus-heated polymer into
particles; and
c) solidifying the thus-divided particles to form solidified polymer
particles of average particle size of about 0.1 to about 3 mm;
whereby substantially no fibers are formed among the solidified particles.
2. The process of claim 1, wherein the polymer has an initial inherent
viscosity not exceeding about 0.6 dl/g when measured at the temperature of
about 30.degree. C. in chloroform or hexafluoroisopropanol.
3. The process of claim 1, wherein the polymer has an initial inherent
viscosity above about 0.6 dl/g when measured at a temperature of about
30.degree. C. in chloroform or hexafluoroisopropanol, and further
comprising:
treating the polymer so that the viscosity of the polymer is reduced to a
level not exceeding about 0.6 dl/g when measured at 30.degree. C. in
chloroform or hexafluoroisopropanol and then heating the polymer in
accordance with step (a).
4. The process of claim 3, wherein the polymer is treated by heating to
cause the polymer to degrade.
5. The process of claim 4, wherein the polymer is heated in the presence of
moisture to cause hydrolysis.
6. The process of claim 1, wherein the polymer is divided by extrusion
through a capillary.
7. The process of claim 6, wherein the capillary has a minimum diameter
from about 0.010 to about 0.002 inch.
8. The process of claim 7, wherein the minimum capillary diameter is from
about 0.009 to about 0.003 inch.
9. The process of claim 8, wherein the minimum capillary diameter is from
about 0.008 to about 0.004 inch.
10. The process of claim 6, wherein the polymer is extruded through the
capillary at a rate of about 15 to about 0.3 inch/min.
11. The process of claim 10, wherein the extrusion rate is about 12 to
about 0.5 inch/min.
12. The process of claim 11, wherein the extrusion rate is about 10 to
about 1 inch/min.
13. The process of claim 1, wherein the polymer is divided by being sprayed
through a nozzle.
14. The process of claim 1, wherein the polymer particles are solidified by
being introduced into a liquid which is immiscible with the polymer and
which freezes the polymer particles on contact therewith.
15. The process of claim 14, wherein the solidified polymer particles are
insoluble in the liquid.
16. The process of claim 1, wherein the polymer particles are solidified by
falling freely through air.
17. The process of claim 1, wherein the particles fall a distance of at
least about 40 cm. through the air.
18. The process of claim 1, wherein the average particle size of the
solidified particles is from about 0.2 to about 1.5 mm.
19. The process of claim 18, wherein the average particle size of the
solidified particles is from about 0.3 to about 1.0 mm.
20. The process of claim 1, wherein the average particle size of the
solidified particles is equal to or greater than about 0.42 mm.
21. The process of claim 1, wherein the polymer is heated to a temperature
of from about 100.degree. to about 300.degree. C.
22. The process of claim 21, wherein the polymer is heated to a temperature
of from about 170.degree. to about 270.degree. C.
23. The process of claim 22, wherein the polymer is heated to a temperature
of from about 220.degree. to about 250.degree. C.
24. A process for preparing particles of bioabsorbable polymer, comprising:
a) heating to a temperature of from about 60.degree. to about 300.degree.
C., a polymer derived from monomers selected from the group consisting of
glycolic acid, lactic acid, dioxanone, e-caprolactone and trimethylene
carbonate and having an inherent viscosity between about 0.5 and about 0.6
dl/g when measured at a temperature of about 30.degree. C. in chloroform
or hexafluoroisopropanol to form a molten or flowable mass;
b) dividing the molten or flowable mass of thus-heated polymer into
particles, wherein the polymer is divided by being applied onto a rotary
atomizer upon whose surface the molten polymer breaks up into particles
which are thrust away from the axis of the rotary atomizer; and
c) solidifying the thus-divided particles to form solidified polymer
particles of average particle size of about 0.1 to about 3 mm;
whereby substantially no fibers are formed among the solidified particles.
25. The process of claim 24, wherein the average particles size of the
solidified particles is equal to or greater than about 0.42 mm.
26. A process for preparing particles of bioabsorbable polymer, comprising:
a) heating to a temperature from about 60.degree. to about 300.degree. C.,
a polymer derived from monomers selected from the group consisting of
glycolic acid, lactic acid, dioxanone, e-caprolactone and trimethylene
carbonate and having an inherent viscosity between about 0.2 and about 0.6
dl/g when measured at a temperature of about 30.degree. C. in chloroform
or hexafluoroisopropanol, to form a molten or flowable mass;
b) dividing the molten or flowable mass of thus-heated polymer into
particles; and
c) solidifying the thus-divided particles by introducing the particles into
a liquid which is immiscible with the polymer and which freezes the
polymer particles on contact therewith, the liquid being selected from the
group consisting of liquid nitrogen, and mixtures of solid carbon dioxide
and a liquid, to form solidified polymer particles of average particle
size of about 0.1 to about 3 mm;
whereby substantially no fibers are formed among the solidified particles.
27. Process for preparing particles of bioabsorbable polymer, consisting
essentially of the steps of:
a) heating to a temperature from about 60.degree. to about 300.degree. C.,
a polymer derived from monomers selected from the group consisting of
glycolic acid, lactic acid, dioxanone, e-caprolactone and trimethylene
carbonate and having an inherent viscosity between about 0.5 and about 0.6
dl/g when measured at a temperature of about 30.degree. C. in chloroform
or hexafluoroisopropanol, to form a molten or flowable mass;
b) dividing the molten or flowable mass of thus-heated polymer into
particles; and
c) solidifying the thus-divided particles to form solidified polymer
particles of average particle size of about 0.42 to about 3 mm;
wherein substantially no fibers are formed among the solidified particles.
Description
BACKGROUND OF THE INVENTION
This invention relates to a process for preparing particles of polymer,
e.g., spheroidal particulates or beads of the bioabsorbable variety,
employing various individual atomization techniques such as melt extrusion
and/or rotary atomization. The particles are useful, inter alia, in the
repair of damaged or defective bone.
The medical use of polymer particles including those of the bioabsorbable
variety are known, inter alia, from U.S. Pat. Nos. 3,882,858; 4,535,485;
4,547,390; 4,643,735; and 4,663,447. There has been an increase in
interest in utilizing both bioabsorbable and non-absorbable particles to
facilitate bone or fibrous tissue repair/reconstruction.
A number of processes are known for preparing finely divided polymeric
particles, e.g., mechanical grinding, solvent precipitation, dispersion,
and spray atomization of solutions or slurries. U.S. patent application
Ser. No. 654,219, filed Feb. 12, 1991, now U.S. Pat. No. 5,143,662
describes producing particles of polymer by subjecting the polymer to
rotary atomization. In rotary atomization, the polymer is applied to a
rotation bell, cup or disk with mechanical forces predominating in the
breakup of the polymer into particles. U.S. patent application Ser. No.
503,264, filed Apr. 2, 1990 and now U.S. Pat. No. 5,102,983 issued Apr. 7,
1992 describes a process for preparing foamed, bioabsorbable polymer
particles by a freeze-drying technique.
Processes which form microspheres of absorbable material less than or equal
to 0.2 mm in diameter for use in controlled release of drugs, are
well-known. Such spheres have generally been formed by a solvent
evaporation technique. Alternatively, polymeric microspheres, e.g., beads,
of average particle size greater than or equal to 0.2 mm in diameter can
be formed by an emulsion polymerization process. Such emulsion
polymerization has been successfully utilized to form beads of
polymethylmethacrylate and styrene.
For medical applications, it is often desirable to control not only the
particle size distribution of the polymeric particles but level of fibers
which are present as well.
SUMMARY OF THE INVENTION
The present invention is directed to a process for preparing particles from
a polymer having fiber-forming properties comprising:
a) heating a polymer having an inherent viscosity not exceeding about 0.6
dl/g when measured at a temperature of about 30.degree. C. in chloroform
or hexafluoroisopropanol (HFIP);
b) dividing the thus-heated polymer into particles; and
c) solidifying the polymer particles,
such that substantially no fibers are formed among the solidified
particles.
When the conditions of the present invention are followed, particles of
polymer of substantially uniform size, e.g., microspheres of about 0.1 to
about 3.0 mm average size (in diameter) can be prepared from polymeric
substances, while fiber forming tendencies of the polymer are suppressed.
In other words, the fiber forming tendency of the polymeric material,
which is believed to relate to the surface tension exhibited by the
polymer, is inhibited according to the present invention such that
substantially no fibers are produced among the particles that are
prepared. As used herein, the term "fiber" refers to materials which may
be characterized as having a denier (see, e.g., Plastics Terms Glossary,
Fourth Edition, Phillips Chemical Company, Bartlesville, Oklahoma).
The particles are preferably formed into spheres which can be used as a
packing or molded part in dental or orthopedic applications in which a
bony defect is filled with material. Such material then acts as a scaffold
for new bony ingrowth while, in the case of bioabsorbable particles, being
resorbed by the body, leaving behind a fully healed bone tissue structure.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will be described in greater detail below, with
reference to the accompanying drawings in which:
FIG. 1 is a perspective view of an extrusion die adapter which can be
utilized in accordance with the present invention; and,
FIG. 2 is a perspective view of another extrusion die adapter which can be
utilized in accordance with the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In order to minimize the formation of fibers during the process of the
present invention, a polymer is selected for processing which has an
inherent viscosity not exceeding about 0.6 dl/g when measured at a
temperature of about 30.degree. C. in chloroform or HFIP (concentration of
the polymer during this measurement is about 0.25 g/dl). HFIP is generally
used as the measuring solvent when glycolide content exceeds about 40 mole
percent of the overall polymer being measured. Preferably, the polymer has
an inherent viscosity, when measured under these conditions, of about 0.2
to about 0.5 dl/g, more preferably about 0.25 to about 0 0.45 dl/g.
It should be noted that the polymer can have an initial inherent viscosity
within the levels set forth above. Alternatively, the polymer can have an
initial inherent viscosity exceeding about 0.6 dl/g when measured under
the above conditions and then can be treated, e.g., heated, to cause
degradation of the polymer, such as by hydrolysis (when heated in the
presence of moisture), to reduce the viscosity to the levels set forth
above. The polymer can then be further heated in accordance with the
heating step of the present invention.
While not being bound by any particular theory on physical properties, it
is believed that the polymer possessing an inherent viscosity not
exceeding about 0.6 dl/g when measured under the above conditions,
exhibits a reduced tendency to form fibers because of a physical attribute
associated with the polymer, e.g., an increased surface tension and/or
reduced chain lengths of individual polymer chains relative to higher
inherent viscosity materials. The inherent viscosity is a function of,
among other factors, the molecular weight of a polymer. Accordingly, the
inherent viscosity of the polymer can be controlled by selecting a polymer
having an appropriate molecular weight.
The polymer is preferably bioabsorbable and can be derived from
polyglycolic acid, glycolide, lactic acid, lactide, dioxanone,
e-caprolactone, trimethylene carbonate, etc., and various combinations of
these and related monomers. Polymers of this type are known in the art,
principally as materials for the fabrication of such surgical devices as
sutures, wound clips, and the like, as disclosed, e.g., in U.S. Pat. Nos.
2,668,162; 2,703,316; 2,758,987; 3,225,766; 3,297,033; 3,422,181;
3,531,561; 3,565,077; 3,565,869; 3,620,218; 3,626,948; 3,636,956;
3,736,646; 3,772,420; 3,773,919; 3,792,010; 3,797,499; 3,839,297;
3,867,190; 3,878,284; 3,982,543; 4,047,533; 4,060,089; 4,137,921;
4,157,437; 4,234,775; 4,237,920; 4,300,565; and, 4,523,591; U.K. Patent
No. 779,291; D. K. Gliding et al., "Biodegradable polymers for use in
surgery - - polyglycolic/poly(lactic acid) homo- and co-polymers: 1",
Polymer, Volume 20, pages 1459-1464 (1979), and D. F. Williams (ed.),
Biocompatibility of Clinical Implant Materials, Vol. II, ch. 9:
"Biodegradable Polymers" (1981). Copolymers of glycolide and lactide with
or without additional monomers are preferred and of these glycolidelactide
copolymers are most preferred.
The present invention may also be practiced on non-absorbable polymeric
materials having fiber-forming properties such as nylon, polyester,
polypropylene, polytetrafluoroethylene (PTFE), polyethylene terephthalate
(Dacron), etc.
According to the present invention, the polymeric material is heated so as
to produce a flowable mass. The polymer is preferably heated to a
temperature from about 60.degree. C. to about 300.degree. C. More
particularly, the temperature to which the polymeric material will be
heated, will depend on the melt characteristics of the polymer selected.
For example, for a glycolide/lactide copolymer, the system is heated to a
temperature of from about 100.degree. to about 300.degree. C., preferably
from about 170.degree. C. to about 270.degree. C., and most preferably
from about 220.degree. C. to about 250.degree. C. For polymers having
lower melting points, e.g., polycaprolactone, lower temperatures may be
employed, e.g., about 60.degree. C., whereas higher temperature may be
required for materials having higher melting points.
After heating the polymer, the heated molten polymer is divided into
particles with the molten particles then being solidified. The polymer is
divided and solidified into the particles such that an average particle
size (diameter) of the particles when solidified will be from about 0.1 to
about 3 mm, more preferably from about 0.2 mm to about 1.5 mm, and most
preferably from about 0.3 to about 1.0 mm.
In this regard, the molten polymer can be divided, e.g., into droplets, by
being extruded through a capillary provided in an extrusion die of
extrusion apparatus. Suitable extrusion apparatus which can be utilized in
accordance with the present invention are described in G. A. Kruder,
"Extrusion", Encyclopedia of Polymer Science and Engineering (Second
Edition), Volume 6, pages 571-631, and in P. N. Richardson, "Plastics
Processing", Encyclopedia of Chemical Technology (Third Edition), Volume
18, pages 185-189. Any part of the extrusion apparatus such as the
extruder screw or the capillary die can be heated to the appropriate
temperature in order to heat the polymer.
As the extrusion apparatus, an Instron Rheometer available from the Instron
Corp. of Canton, Massachusetts 02021 can be used. The Instron Rheometer
has an extrusion barrel of about 20 cm.sup.3 capacity and which is
provided with a capillary die at the bottom thereof. The barrel is heated
to the appropriate temperature and then loaded with the polymer, which is
forced down through the capillary die by means of a plunger extending into
the barrel.
Extrusion can be carried out through a capillary die adapter 1 illustrated
in FIG. 1, having a capillary 2 of substantially constant inner diameter
h. Alternatively, a capillary die adapter 20 of FIG. 2 can be utilized,
which comprises a capillary 12 of narrowing inner diameter. Rate of
extrusion and diameter size of the capillary determine ultimate particle
size of solidified polymer particles. In particular, the capillary has a
narrowest inner diameter of preferably about 0,010 to about 0.002 inch,
more preferably about 0.009 to about 0.003 inch, and most preferably about
0.008 to about 0.004 inch. The polymer is extruded through the capillary
preferably at a rate of about 15 to about 0.3 inch/min., more preferably
at a rate of about 12 to about 0.5 inch/min., and most preferably at a
rate of about 10 to about 1 inch/min.
Alternatively, the molten polymer can be divided into droplets, after being
heated, by being sprayed through a spray nozzle. The spray nozzle itself
can be heated to an appropriate temperature level in order to heat the
polymer.
Furthermore the polymer can also be divided, after heating, by being
applied onto a rotary atomizer upon whose surface the polymer breaks up
into particles which are thrust away from the axis of the rotary atomizer.
Suitable rotary atomizers which can be utilized in accordance with the
present invention include those disclosed in U.S. Pat. Nos. 4,256,677;
3,741,703; and 3,743,464. A circular rotating element, e.g. a spinning
disk of the rotary atomizer, can be flat, convex, concave, or even
bell-shaped, and can contain protruding vanes on a surface thereof.
The size of the spinning disk itself and the rpm., i.e. rate of rotation,
can be interrelated to provide the optimum centrifugal acceleration for
the formation of the particles of bioabsorbable polymer. Variations of
this centrifugal acceleration will affect the ultimate size of the
particles that are formed. The revolutions of the spinning disk are
controlled within a range of preferably about 100 to about 1000 rpm., more
preferably within a range of about 130 to about 850 rpm., and most
preferably within a range of about 160 to about 700 rpm. Furthermore, the
disk itself is preferably between about 66 and about 86 cm. in diameter,
more preferably between about 71 and about 81 cm. in diameter, and most
preferably between about 75 and about 77 cm. in diameter. The
instantaneous velocity of the disk is preferably controlled within a range
of about 4 to about 40 m./sec., more preferably within a range of about 5
to about 35 m./sec., and most preferably within a range of about 6 to
about 28 m./sec.
The bioabsorbable polymer is supplied in the form of a thin film onto a
surface of the spinning disk of the rotary atomizer, whereby the
centrifugal acceleration breaks the thin film into particles of the
bioabsorbable polymer. Preferably, this film of polymer is applied about
0.01 to about 3.5 mm. thick on the spinning disk, more preferably about
0.1 to about 3.2 mm. thick, and most preferably of about 1.0 to about 3.0
mm. thick. Surface tension will cause the resulting particles of broken up
polymer to ultimately harden into particles which are spheroidal or in the
shape of beads, as these particles are radially discharged from the disk,
i.e. fall off the edge of the rotary spinning disk of the rotary atomizer
and are cooled. Varying the film thickness on the spinning disk or varying
the feed rate of the flowable bioabsorbable polymer affects particle size,
with the thinnest film causing the smallest particles to be formed.
Clearly, the molten polymer can be divided by other means within the
context of the present invention. Once divided, the molten particles of
polymer are solidified. Solidification can be carried out by allowing the
extruded, sprayed or atomized particles to fall into a liquid which is
immiscible with the molten polymer, which freezes the polymer particles on
contact therewith, and in which the solidified polymer is not soluble. The
freezing liquid can be, e.g., liquid nitrogen, and mixtures of solid
carbon dioxide and a liquid such as acetone, pentane, etc. In general, the
temperature of the freezing liquid is advantageously at least about
10.degree. C. below the freezing temperature of the polymer particles. The
lower the temperature of the freezing liquid, the faster the polymer
particles will freeze solid therein. It is desirable to maintain a certain
particle configuration, e.g., spheres upon freezing, and therefore rapid,
even instantaneous freezing is called for. This can be conveniently
achieved employing a freezing liquid such as liquid nitrogen.
The particles of frozen polymer can be recovered from the freezing liquid
employing any suitable means, e.g., draining, straining, filtering,
decanting or centrifuging, and the like. This operation is conducted at or
below the melting point of the frozen polymeric particles to maintain the
particles in the frozen state.
Alternatively, the polymeric particles can be solidified by falling freely
through the air. The particles are allowed to fall a distance of at least
about 40 cm. through the air, whereby the particles are sufficiently
cooled before striking a collecting unit so that the particles will not
stick together upon striking the collecting unit. More specifically, the
particles are allowed to fall a distance of preferably about 190 to about
254 cm., more preferably about 200 to about 240 cm., and most preferably
about 215 to about 230 cm. before striking the collecting unit. The
collecting unit may be provided, e.g., as disclosed in U.S. Pat. Nos.
4,256,677 and 3,743,464.
The particles or beads formed of bioabsorbable or non-absorbable polymers
can be used as filler in a surgical prosthesis, i.e. for implantation in a
cavity provided in bone or fibrous tissue to encourage regrowth and
regeneration of the tissue. The particles of the bioabsorbable polymer are
absorbed by the body at a predictable rate allowing tissue or bony
ingrowth as absorption takes place. The rate of absorption is
characteristic of the polymer utilized. Thus, e.g., a glycolide-lactide
copolymer will often completely resorb within six months in contrast to
about two years for polyglycolide homopolymer. Both the bioabsorbable and
nonabsorbable polymeric particles are readily molded to fill cavities or
other contours. The beads can be heated to softening temperature, e g, to
about 60.degree. C., at which temperature they can be worked and shaped.
Any required drug, medicinal material, or growth factor can be incorporated
into the polymer prior to processing, e.g. by addition to the polymer in
the customary amounts so that at the conclusion of the polymeric particle
manufacturing process herein, the particles will contain a predetermined
amount of one or more of such substances.
Thus, it is within the scope of this invention to incorporate one or more
medico-surgically useful substances into the particles, e.g., those which
accelerate or beneficially modify the healing process when particles are
applied to a surgical repair site. For example, the polymer particles can
carry a therapeutic agent which will be deposited at the repair site. The
therapeutic agent can be chosen for its antimicrobial properties,
capability for promoting repair or reconstruction and/or new tissue growth
or for specific indications such as thrombosis. Antimicrobial agents such
as broad spectrum antibiotics (gentamicin sulphate, erythromycin or
derivatized glycopeptides) which are slowly released into the tissue can
be applied in this manner to aid in combating clinical and sub-clinical
infections in a tissue repair site.
To promote repair and/or tissue growth, one or several growth promoting
factors can be introduced into the particles, e.g., fibroblast growth
factor, bone growth factor, epidermal growth factor, platelet derived
growth factor, macrophage derived growth factor, alveolar derived growth
factor, monocyte derived growth factor, magainin, and so forth. Some
therapeutic indications are: glycerol with tissue or kidney plasminogen
activator to cause thrombosis, superoxide dismutase to scavenge tissue
damaging free radicals, tumor necrosis factor for cancer therapy or colony
stimulating factor and interferon, interleukin-2 or other lymphokine to
enhance the immune system.
The present invention will be explained in greater detail, by way of the
following examples:
EXAMPLE 1
A capillary die adapter 1 of FIG. 1 having the following dimensions:
D=0.730 inch; L.sub.1 =1/8 inch; L.sub.2 =1/8 inch; d=0.300 inch; and
h=0.016 inch, was provided on a barrel of an Instron Rheometer extrusion
apparatus. The extrusion apparatus, including the barrel and the adapter
1, was heated to 250.degree. C. and then loaded with 25/75 mole percent
glycolide/lactide copolymer having an inherent viscosity, measured at
30.degree. C. in HFIP and at a concentration of 0.25 g/dl, of 0.49 dl/g.
This copolymer was maintained in the barrel of the extrusion apparatus for
5 minutes and then extruded through capillary 2 of the die adapter 1 at a
rate of 0.3 inch/min., whereby droplets of the polymer were formed. These
droplets of the polymer were allowed to fall from the die adapter 1 a
distance of 40 cm. and into a vat of liquid nitrogen at a temperature of
-196.degree. C., with the droplets of polymer thereby solidifying into
beads. The beads were collected from the liquid nitrogen, classified, and
were found to have an average diameter of 3 mm. The solidified polymer
thus formed was substantially free of fibers.
This procedure was repeated, but with the 25/75 mole percent
glycolide/lactide copolymer being exposed to air for 72 hours before being
added to the heated extruder barrel. Clearer beads of a range of particle
size of 2.8-3.1 mm were produced, the solidified polymer being
substantially free of fibers.
EXAMPLE 2
The procedure of Example 1 was repeated, but with a die adapter disc 10 of
FIG. 2 having a capillary 12 necking down from an inner entrance diameter
D' of 1.25 mm to an inner exit diameter d' of 0.008 inch, with the
extrusion apparatus including the adapter 10 being heated to a temperature
of 225.degree. C., and with respective rates of extrusion of 1 inch/min.,
3 inch/min., and 10 inch/min. respectively for equal extruded amounts of
the 25/75 mole percent glycolide/lactide copolymer having an inherent
viscosity of 0.5 dl/g measured at 30.degree. C. in HFIP and at a
concentration of 0.25 g/dl. The extrudate formed a stream that broke into
droplets upon exiting from the adapter 10, with the falling droplets being
directed into a bucket of liquid nitrogen at -296.degree. C. with
stirring. A total of 15.65 g of beads (the product being substantially
fiber free) was collected from these three combined runs and then
classified, with the distribution being reported in Table II below:
TABLE II
______________________________________
Weight (g) of Particles
% of Particles
Sieve No.*
Retained Thereon
Retained Thereon
______________________________________
14 7.29 46.58
16 4.23 27.03
18 2.25 14.38
20 0.72 4.60
25 0.63 4.02
40 0.53 3.39
Total 15.65 g Total 100.00%
______________________________________
*a No. 14 sieve has openings of 1.41 mm;
a No. 16 sieve has openings of 1.19 mm;
a No. 18 sieve has openings of 1.00 mm;
a No. 20 sieve has openings of 0.841 mm;
a No. 25 sieve has openings of 0.707 mm; and
a No. 40 sieve has openings of 0.420 mm.
EXAMPLE 3
The procedure of Example 2 was repeated but with all molten polymer being
extruded at a rate of 1 inch/min. A total of 6.96 g of beads was collected
and then classified, with the distribution being reported in Table III
below:
TABLE III
______________________________________
Weight (g) of Particles
% Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
14 0.84 12.07
16 1.71 24.57
18 1.99 28.59
20 1.83 26.29
25 0.25 3.59
40 0.30 4.31
Passed Through 40 0.04 0.58
Total 6.96 g Total 100.00%
______________________________________
EXAMPLE 4
The procedure of Example 2 was repeated, but with all molten polymer being
extruded at a rate of 3 inches/min. A total of 13.03 g of beads was
collected and then classified, with the distribution being reported in
Table IV below:
TABLE IV
______________________________________
Weight (g) of Particles
% Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
14 9.93 76.21
16 2.30 17.65
18 0.64 4.91
20 0.06 0.46
25 0.07 0.54
40 0.02 0.15
Passed Through 40 0.01 0.08
Total 13.03 g Total 100.00%
______________________________________
EXAMPLE 5
The procedure of Example 2 was repeated, but with all molten polymer being
extruded at a rate of 10 inches/min. A total of 19.62 g of beads was
collected and then classified, with the distribution being reported in
Table V below:
TABLE V
______________________________________
Weight (g) of
Particles % Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
14 13.49 68.76
16 3.38 17.23
18 1.35 6.88
20 0.63 3.21
25 0.38 1.94
40 0.32 1.63
Passed Through 40 0.07 0.36
Total 19.62 g Total 100.01%**
______________________________________
**100.01% value due to rounding of significant figures.
EXAMPLE 6
The procedure of Example 3 was repeated in its entirety, but with the
molten polymer being extruded through die adapter 10 having an extrusion
channel 12 necking down from an entrance diameter D' of 1.25 mm to a
minimum a diameter d' of 0.006 inch at the outlet thereof. A total of 5.94
g of beads was collected and then classified, with the distribution being
reported in Table VI below:
TABLE VI
______________________________________
Weight (g) of Particles
% Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
14 0.70 11.78
16 1.09 18.35
18 1.45 24.41
20 1.17 19.70
25 0.88 14.82
40 0.58 9.76
Passed Through 40 0.07 1.18
Total 5.94 g Total 100.00%
______________________________________
EXAMPLE 7
The procedure of Example 4 was repeated in its entirety, but with the
molten polymer being extruded through die adapter 10 having an extrusion
channel 12 necking down from an entrance diameter D' of 1.25 mm to a
minimum diameter d' of 0.006 inch at the outlet thereof. A total of 8.49 g
of beads was collected and then classified, with the distribution being
reported in Table VII below:
TABLE VII
______________________________________
Weight (g) of Particles
% Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
14 2.58 30.39
16 2.89 34.04
18 2.15 25.32
20 0.39 4.59
25 0.23 2.71
40 0.18 2.12
Passed Through 40 0.07 0.83
Total 8.49 g Total 100.00%
______________________________________
EXAMPLE 8
The procedure of Example 5 was repeated in its entirety, but with the
molten polymer being extruded through a die adapter 10 having an extrusion
channel 12 necking down from an entrance diameter D' of 1.25 mm to a
minimum diameter d' of 0.006 inch at the outlet thereof. A total of 14.5 g
of beads was collected and then classified, with the distribution being
reported in Table VIII below:
TABLE VIII
______________________________________
Weight (g) of Particles
% Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
14 5.63 38.83
16 5.06 34.90
18 1.52 10.48
20 0.72 4.96
25 0.82 5.66
40 0.63 4.34
Passed Through 40 0.12 0.83
Total 14.50 g Total 100.00%
______________________________________
EXAMPLE 9
The procedure of Example 2 was repeated in its entirety, but with the
molten polymer additionally being stirred before extrusion. A total of
56.77 g of beads was collected and then classified, with the distribution
being reported in Table IX below:
TABLE IX
______________________________________
Weight (g) of Particles
% of Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
14 22.36 39.39
16 17.00 29.95
18 11.78 20.75
20 1.99 3.51
25 1.66 2.92
40 1.62 2.85
Passed Through 40 0.36 0.63
Total 56.77 g Total 100.00%
______________________________________
EXAMPLE 10
The procedure of Example 2 was repeated in its entirety, but with a die 10
having a channel 12 necking down from an entrance diameter D' of 1.25 mm
to a minimum exit diameter d' of 0.006 inch. A total of 7.61 g of beads
was collected and then classified, with the distribution being reported in
Table X below:
TABLE X
______________________________________
Weight (g) of Particles
% Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
20 0.32 4.20
25 3.72 48.88
40 3.39 44.55
Passed Through 40 0.18 2.37
Total 7.61 g Total 100.00%
______________________________________
EXAMPLE 11
The procedure of Example 7 was repeated in its entirety, but with
polyglycolic acid (PGA), having an inherent viscosity of 0.25 dl/g
measured at 30.degree. C. in HFIP and at a concentration of 0.25 g/dl,
being heated to 225.degree. C. and then being extruded at a rate of 3
inch/min. A total of 10.04 g of PGA beads was collected and then
classified, with the distribution being reported in Table XI below:
TABLE XI
______________________________________
Weight (g) of Particles
% Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
20 6.30 62.75
25 1.80 17.93
40 1.70 16.93
Passed Through 40 0.24 2.39
Total 10.04 g Total 100.00%
______________________________________
EXAMPLE 12
The procedure of Example 11 was repeated, but with the polyglycolic acid
(PGA) being heated to 240.degree. C. and then being extruded (the PGA had
an inherent viscosity of 0.25 dl/g at 30.degree. C. in HFIP and at a
concentration of 0.25 g/dl). A total of 5.52 g of PGA beads was collected
and then classified, with the results being reported in Table XII below:
TABLE XII
______________________________________
Weight (g) of Particles
% Particles
Sieve No. Retained Thereon
Retained Thereon
______________________________________
20 4.90 88.77
25 0.22 3.98
40 0.31 5.62
Passed Through 40 0.09 1.63
Total 5.52 g Total 100.00%
______________________________________
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